Variant 14-59745983-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021136.3(RTN1):c.740G>A(p.Gly247Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,982 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.024 ( 139 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 136 hom. )

Consequence

RTN1
NM_021136.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.166

Variant links:

Genes affected

RTN1 (HGNC:10467): (reticulon 1) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

RTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017468333).

BP6

Variant 14-59745983-C-T is Benign according to our data. Variant chr14-59745983-C-T is described in ClinVar as [Benign]. Clinvar id is 781131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RTN1	NM_021136.3 linkuse as main transcript	c.740G>A	p.Gly247Glu	missense_variant	2/9	ENST00000267484.10	NP_066959.1
RTN1	XM_011537063.4 linkuse as main transcript	c.740G>A	p.Gly247Glu	missense_variant	2/4		XP_011535365.1
RTN1	XM_047431674.1 linkuse as main transcript	c.740G>A	p.Gly247Glu	missense_variant	2/4		XP_047287630.1
RTN1	XR_007064042.1 linkuse as main transcript	n.886G>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10 linkuse as main transcript	c.740G>A	p.Gly247Glu	missense_variant	2/9	1	NM_021136.3	ENSP00000267484		Q16799-1

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3677

AN:

152050

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0838

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00667

AC:

1676

AN:

251308

Hom.:

AF XY:

0.00496

AC XY:

674

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0848

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.00695

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00276

AC:

4032

AN:

1461814

Hom.:

136

Cov.:

AF XY:

0.00249

AC XY:

1812

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0872

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.00654

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.00654

GnomAD4 genome

AF:

0.0242

AC:

3686

AN:

152168

Hom.:

139

Cov.:

AF XY:

0.0235

AC XY:

1748

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0838

Gnomad4 AMR

AF:

0.00798

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.0275

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0826

AC:

364

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00806

AC:

979

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0065

T;T

Eigen

Benign

0.078

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.95

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.099

Sift

Benign

0.42

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.99

D;.

Vest4

0.36

MVP

0.082

MPC

0.35

ClinPred

0.021

GERP RS

3.7

Varity_R

0.058

gMVP

0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over